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Benefit–Risk Assessment of Psychotropic Drugs in Older Patients with Chronic Obstructive Pulmonary Disease

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Abstract

Depression, anxiety, and other mental health disorders, including bipolar disorder and schizophrenia, occur commonly in older adults with chronic obstructive pulmonary disease (COPD), and they are often inadequately treated. We review the available evidence for benefits and risks of pharmacologic treatments (e.g. selective serotonin reuptake inhibitors [SSRIs], serotonin-noradrenaline reuptake inhibitors [SNRIs], tricyclic antidepressants [TCAs], antipsychotic drugs, and benzodiazepines) for common mental illnesses in older persons with COPD. Evidence to use both SSRIs/SNRIs and TCAs from randomized controlled trials is uncertain for treating major depression in patients with COPD. However, population-based findings indicate that they are widely used, and this valuable intervention (preferably SSRIs/SNRIs) should not be denied for selected patients after evaluating potential risks and benefits, especially patients presenting with major depression and suicidal ideation, when a collaborative-care approach is being used. Although there is some evidence for the short-term use of benzodiazepines for treating insomnia, breathlessness, and anxiety in patients with COPD, their long-term use should be closely monitored or avoided to reduce the increased rate of major adverse events. Currently, there are only limited data on the use of antipsychotic drugs for managing schizophrenia or bipolar disorder in older patients with COPD. Hence, clinicians should use extra caution when prescribing antipsychotic agents and be vigilant for symptoms of acute respiratory failure and other adverse effects. Psychotropic medications are clearly beneficial for younger, healthy persons with depression and anxiety; however, the risk–benefit calculation is not so clear for treating psychological problems, schizophrenia, and bipolar disorder in older adults with COPD, given older-adult sensitivity to medications and the mixed findings of relatively few controlled trials.

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References

  1. Yohannes AM, Willgoss TG, Baldwin RC, Connolly MJ. Depression and anxiety in chronic heart failure and chronic obstructive pulmonary disease: prevalence, relevance, clinical implications and management principles. Int J Geriatr Psychiatry. 2010;25:1209–21.

    Article  CAS  PubMed  Google Scholar 

  2. Maurer J, Rebbapragada V, Borson S, Goldstein R, Kunik ME, Yohannes AM, et al. Anxiety and depression in COPD: current understanding, unanswered questions, and research needs. Chest. 2008;134(Suppl):43S-56S.

    Article  PubMed  Google Scholar 

  3. Singh G, Zhang W, Kuo Y-F, Sharma G. Association of psychological disorders with 30-day readmission rates in patients with COPD. Chest. 2016;149(4):905–15.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Iyer AS, Bhatt SP, Garner JJ, Wells JM, Trevor JL, Patel NM, et al. Depression is associated with readmission for acute exacerbation of chronic obstructive pulmonary disease. Ann Am Thorac Soc. 2016;13(2):197–203.

    PubMed  PubMed Central  Google Scholar 

  5. Strang S, Ekberg-Jansson A, Henoch I. Experience of anxiety among patients with severe COPD: a qualitative in-depth interview study. Palliat Support Care. 2014;12(6):465–72.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Vardar-Yagli N, Calik-Kutukcu E, Saglam M, Inal-Ince D, Arikan H, Coplu L. The relationship between fear of movement, pain and fatigue severity dyspnea and comorbidities in patients with chronic obstructive pulmonary disease. Diabil Rehabil. 2019;41(18):2159–63.

    Article  Google Scholar 

  7. Matthew AR, Hogarth L, Leventhal AM, Cook JW, Hitsman B. Cigarette smoking and depression comorbidity: systematic review and proposed theoretical model. Addiction. 2016;112:401–12.

    Article  Google Scholar 

  8. Prochaska JJ, Das S, Young-Wolff KC. Smoking, mental illness, and public health. Annu Rev Public Health. 2017;38:165–85.

    Article  PubMed  Google Scholar 

  9. Wang S, Blazer DG. Depression and cognition in the elderly. Annu Rev Clin Psychol. 2015;11:331–60.

    Article  PubMed  Google Scholar 

  10. Yohannes AM, Baldwin RC, Connolly MJ. Mood disorders in elderly patients with chronic obstructive pulmonary disease. Rev Clin Geronotol. 2000;10(2):193–202.

    Article  Google Scholar 

  11. Lawrence D, Mitrou F, Zubrick SR. Smoking and mental illness: results from population surveys in Australia and the United States. BMC Public Health. 2009;9:285.

    Article  PubMed  PubMed Central  Google Scholar 

  12. McClave AK, McKnight-Eily LR, Davis SP, Dube SR. Smoking charcteristics of adults with selcted lifetime mental illnesses results from the 2007 National Health Interview Survey. Am J Public Health. 2010;100:2464–72.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Feighner JP. Mechanism of action of antidepressant medications. J Clin Psychiatry. 1999;60(Suppl 4):4–11.

    CAS  PubMed  Google Scholar 

  14. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th edn. Arlington: American Psychiatric Publishing; 2013. https://www.psychiatry.org/psychiatrists/practice/dsm. Accessed 4 Jan 2022

  15. Atlantis E, Fahey P, Cochrane B, Smith S. Bidirectional associations between clinically relevant depression or anxiety and COPD: a systematic review and meta-analysis. Chest. 2013;144(3):766–77.

    Article  PubMed  Google Scholar 

  16. Yohannes AM, Mullerova H, Hanania NA, et al. Long-term course of depression trajectories in patients with COPD: a 3-year follow-up analysis of the evaluation of COPD longitudinally to identify predictive surrogate endpoints cohort. Chest. 2016;149(4):916–26.

    Article  PubMed  Google Scholar 

  17. NICE guideline. Depression in adults: the treatment and management of depression in adults. 2009. www.nice.org.uk/CG90. Accessed 4 Jan 2022.

  18. Torres GE, Gainetdinov RR, Caron MG. Plasma membrane monoamine trans-porters: structure, regulation and function. Nat Rev Neurosci. 2003;4(1):13–25.

    Article  CAS  PubMed  Google Scholar 

  19. Prekson SH. Clinically relevant pharmacology of selective reuptake inhibitors: an overview with emphasis on pharmacokinetics and effects of oxidative drug metabolism. Clin Pharmacokinet. 1997;32(Suppl 1):1–21.

    Google Scholar 

  20. Suchting R, Tirumalaraju V, Gareeb R, Bockmann T, de Dios C, Aickareth J, et al. Revisiting monoamine oxidase inhibitors for the treatment of depressive disorders: a systematic review and network meta-analysis. J Affect Disord. 2021;282:1153–60.

    Article  CAS  PubMed  Google Scholar 

  21. Pelgrim CE, van den Heuvel JM, Folkerts G, Garssen J, der Zee AHM, Kraneveld AD. Higher prescription of antidepressants and/or anxiolytics among chronic obstructive pulmonary disease. Ther Adv Respir Dis. 2021;15:1–9.

    Article  CAS  Google Scholar 

  22. Vozoris NT, Wang X, Austin PC, Stephenson AL, O’Donnell DE, Gershon AS, et al. Serotonergic antidepressant use and morbidity and mortality among older adults with COPD. Eur Respir J. 2018;52:1800475.

    Article  PubMed  CAS  Google Scholar 

  23. Wei Y-J, Simoni-Wastila L, Albrecht JS, Huang T-Y, Moyo P, Khokhar B, et al. The association of antidepressant treatment with COPD maintenance medication use and adherence in a comorbid medicare population: a longitudinal cohort study. Int J Geriatr Psychiatry. 2017;33:e212–20.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Yohannes AM, Alexopoulos GS. Pharmacological treatment of depression in older patients with chronic obstructive pulmonary disease: impact on the course of the disease and health outcomes. Drugs Aging. 2014;31:483–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Pollok J, van Agteren JEM, Carson-Chahhoud KV. Pharmacological interventions for the treatment of depression in chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2018;12(12): 012346.

    Google Scholar 

  26. Yohannes AM, Newman M, Kunik ME. Psychiatric collaborative care for patients with respiratory disease. Chest. 2019;155:1288–95.

    Article  PubMed  Google Scholar 

  27. Dickerson F, Schroeder J, Katsafanas E, Khushalani S, Origoni AE, Savage C, et al. Cigarette smoking by patients with serious mental illness, 1999–2016: an increasing disparity. Psychiatr Serv. 2017;69(2):147–53.

    Article  PubMed  Google Scholar 

  28. Centers for Disease Control and Prevention. Vital signs: current cigarette smoking among adults aged ≥ 18 years with mental illness—United States, 2009–2011. MMWR. 2013;62(5):81–7.

    Google Scholar 

  29. Zareifopoulos N, Bellou A, Spiropoulou A, Spiropoulos K. Prevalence of comorbid chronic obstructive pulmonary disease in individual suffering from Schizophrenia and bipolar disorder. A systematic review. J Chronic Obstr Pulm Dis. 2019;15(6):612–20.

    Article  Google Scholar 

  30. Hsu J-H, Chien I-C, Lin C-H. Increased risk of chronic obstructive pulmonary disease in patients with bipolar disorder: a population-based study. J Affect Disord. 2017;220:43–8.

    Article  PubMed  Google Scholar 

  31. Tsai P-J, Liao Y-T, Lee CT-C, Hsu C-Y, Hsieh M-H, Tsai C-J, et al. Risk of bipolar disorder in patients with COPD: a population based cohort study. Gen Hosp Psychiatry. 2016;41:6–12.

    Article  PubMed  Google Scholar 

  32. Meltzer HY. Update on typical and atypical antipsychotic drugs. Ann Rev Med. 2013;64:393–406.

    Article  CAS  PubMed  Google Scholar 

  33. Grinchii D, Dremencov E. Mechanism of action of atypical antipsychotic drugs in mood disorders. Int J Mol Sci. 2020;21:9532.

    Article  CAS  PubMed Central  Google Scholar 

  34. Ucok ALP, Gabel W. Side effects of atypical antipsychotics: a brief overview. World Psychiatry. 2008;7(1):58–62.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Wang M-T, Tsai C-L, Lin CW, Yeh C-B, Wang Y-H, Lin HL. Association between antipsychotic agents and risk of acute respiratory failure in patients with chronic obstructive pulmonary disease. JAMA Psychiat. 2017;74(3):252–60.

    Article  Google Scholar 

  36. Jorgensen M, Mainz J, Lange P, Johnson SP. Quality of care and clinical outcomes of chronic obstructive pulmonary disease in patients with schizophrenia. A Danish nationwide study. Int J Qual Health Care. 2018;30(5):351–7.

    Article  PubMed  Google Scholar 

  37. Ferraris A, Blasco B, Tentoni N, Del Olmo F, Barrera F, Angriman F, et al. Antipsychotic use and bloodstream infections among adult patients with chronic obstructive pulmonary disease: a cohort study. J Clin Psychiatry. 2021;82(3):20m13516.

    Article  PubMed  Google Scholar 

  38. Ströhle A, Gensichen J, Domschke K. The diagnosis and treatment of anxiety disorders. Dtsch Arztebl Int. 2018;155(37):611–20. https://doi.org/10.3238/arztebl.2018.0611.

    Article  PubMed  Google Scholar 

  39. Tselebis A, Pachi A, IIias I, Kosmas E, Bratis D, Moussas G, et al. Strategies to improve anxiety and depression in patients with COPD: a mental health perspective. Neuropsychiatr Dis Treat. 2016;12:297–328.

    Article  PubMed  PubMed Central  Google Scholar 

  40. World Health Organization. The ICD-10 classification of mental and behavioural disorders. Diagnostic criteria for research. Geneva: World Health Organization; 1993.

    Google Scholar 

  41. Zigmond AS, Snaith RP. The Hospital Anxiety and Depression Scale. Acta Psychiatr Scand. 1983;67:361–70.

    Article  CAS  PubMed  Google Scholar 

  42. Willgoss TG, Goldbart J, Fatoye F, Yohannes AM. The development and validation of the anxiety inventory for respiratory disease. Chest. 2013;144(5):1587–2159.

    Article  PubMed  Google Scholar 

  43. Goodwin RD, Lavoie KL, Lemeshow AR, et al. Depression, anxiety, and COPD: the unexamined role of nicotine dependence. Nicotine Tob Res. 2012;14:176–83.

    Article  PubMed  Google Scholar 

  44. Fuller-Thomson E, Lacombe-Duncan A. Understanding the association between chronic obstructive pulmonary disease and current anxiety: a population-based study. Chronic Obstr Pulm Dis. 2016;13(5):622–31.

    Article  Google Scholar 

  45. Farach FJ, Pruitt LD, Jun JJ, Jerud AB, Zoellner LA, Roy-Byrne PP. Pharmacological treatment of anxiety disorders: current treatments and future directions. J Anxiety Disord. 2012;26(8):833–43.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Greenblatt HK, Greenblatt DJ. Gabapentin and Pregabalin for the treatment of anxiety disorders. Clin Pharmacol Drug Dev. 2018;7(3):228–32.

    Article  CAS  PubMed  Google Scholar 

  47. Willgoss TG, Yohannes AM. Anxiety disorders in patients with COPD: a systematic review. Respir Care. 2013;58(5):858–66.

    PubMed  Google Scholar 

  48. Stege G, Heijdra YF, van den Elshout FJ, van de Ven MJ, de Bruijn PJ, van Sorge AA, et al. Temazepam 10 mg does not affect breathing and gas exchange in patients with severe normocapnic COPD. Respir Med. 2010;104(4):518–24.

    Article  PubMed  Google Scholar 

  49. Simon ST, Higginson IJ, Booth S, Harding R, Weingärtner V, Bausewein C. Benzodiazepines for the relief of breathlessness in advanced malignant and non-malignant diseases in adults. Cochrane Database Syst Rev. 2016;10(10): CD007354.

    PubMed  Google Scholar 

  50. Woodcock AA, Gross ER, Geddes DM. Drug treatment of breathlessness: contrasting effects of diazepam and promethazine in pink puffers. Br Med J (Clin Res Ed). 1981;283(6287):343–6.

    Article  CAS  Google Scholar 

  51. Man GC, Hsu K, Sproule BJ. Effect of alprazolam on exercise and dyspnea in patients with chronic obstructive pulmonary disease. Chest. 1986;90(6):832–6. https://doi.org/10.1378/chest.90.6.832.

    Article  CAS  PubMed  Google Scholar 

  52. Shivaram U, Cash M, Finch P. Effects of alprazolam on gas exchange, breathing pattern, and lung function in COPD patients with anxiety. Respir Care. 1989;34:196–200.

    Google Scholar 

  53. Morin CM, Benca R. Chronic insomnia. Lancet. 2012;379(9821):1129–41.

    Article  PubMed  Google Scholar 

  54. Lu XM, Zhu JP, Zhou XM. The effect of benzodiazepines on insomnia in patients with chronic obstructive pulmonary disease: a meta-analysis of treatment efficacy and safety. Int J Chron Obstruct Pulmon Dis. 2016;11:675–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Beaupre A, Soucy R, Phillips R, Bourjouin J. Respiratory center output following zopiclone or diazepam administration in patients with pulmonary disease. Respiration. 1988;54(4):235–40.

    Article  CAS  PubMed  Google Scholar 

  56. Chen SJ, Yeh CM, Chao TF, Liu CJ, Wang KL, Chen TJ, et al. The use of benzodiazepine receptor agonists and risk of respiratory failure in patients with chronic obstructive pulmonary disease: a nationwide population-based case-control study. Sleep. 2015;38(7):1045–50.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Vozoris NT, Fischer HD, Wang X, Stephenson AL, Gershon AS, Gruneir A, et al. Benzodiazepine drug use and adverse respiratory outcomes among older adults with COPD. Eur Respir J. 2014;44(2):332–40.

    Article  CAS  PubMed  Google Scholar 

  58. Chen TR, Huang HC, Hsu JH, Ouyang WC, Lin KC. Pharmacological and psychological interventions for generalized anxiety disorder in adults: a network meta-analysis. J Psychiatr Res. 2019;118:73–83.

    Article  PubMed  Google Scholar 

  59. Liao YH, Chen LY, Liao KM, Chen CY. Drug safety of benzodiazepines in Asian patients with chronic obstructive pulmonary disease. Front Pharmacol. 2020;11: 592910.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Chung WS, Lai CY, Lin CL, Kao CH. Adverse respiratory events associated with hypnotics use in patients of chronic obstructive pulmonary disease: a population-based case-control study. Medicine (Baltimore). 2015;94(27): e1110.

    Article  Google Scholar 

  61. Baillargeon J, Singh G, Kuo YF, Raji MA, Westra J, Sharma G. Association of opioid and benzodiazepine use with adverse respiratory events in older adults with chronic obstructive pulmonary disease. Ann Am Thorac Soc. 2019;16(10):1245–51.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Buffett-Jerrott SE, Stewart SH. Cognitive and sedative effects of benzodiazepine use. Curr Pharm Des. 2002;8(1):45–58.

    Article  CAS  PubMed  Google Scholar 

  63. Cabibel V, Alexandre F, Oliver N, Varray A, Héraud N. Psychoactive medications in chronic obstructive pulmonary disease patients: from prevalence to effects on motor command and strength. Respir Med. 2019;159: 105805.

    Article  PubMed  Google Scholar 

  64. Donovan LM, Malte CA, Spece LJ, Griffith MF, Feemster LC, Engelberg RA, et al. Risks of benzodiazepines in chronic obstructive pulmonary disease with comorbid posttraumatic stress disorder. Ann Am Thorac Soc. 2019;16(1):82–90.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Ekström MP, Bornefalk-Hermansson A, Abernethy AP, Currow DC. Safety of benzodiazepines and opioids in very severe respiratory disease: national prospective study. BMJ. 2014;348:g445.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  66. Currow DC, Agar MR. Benzodiazepine prescribing in people with chronic obstructive pulmonary disease: clinical considerations. Drugs Aging. 2020;37:263–70.

    Article  CAS  PubMed  Google Scholar 

  67. Rebar AL, Stanton R, Geard D, Short C, Duncan MJ, Vandelanotte DC. A meta-analysis of the effect of physical activity on depression and anxiety in non-clinical population. Health Psychol Rev. 2015;9:366–78.

    Article  PubMed  Google Scholar 

  68. Yohannes AM, Junkes-Cunha M, Smith J, Vestbo J. Management of dyspnea and anxiety in chronic obstructive pulmonary disease: a critical Review. J Am Med Dir Assoc. 2017;12:1096.e1-1096.e17.

    Article  Google Scholar 

  69. Laurin C, Laovie KL, Bacon SL, Dupuis G, Lacoste G, Cartier A, et al. Sex differences in the prevalence of psychiatric disorders and psychological distress in patients with COPD. Chest. 2007;132(1):148–55.

    Article  PubMed  Google Scholar 

  70. Yohannes AM. Serotonergic antidepressants in COPD: beneficial or harmful. Eur Respir J. 2018;52:1801095.

    Article  PubMed  Google Scholar 

  71. Yohannes AM, Casaburi R, Dryden S, Hanania NA. Predictors of premature discontinuation and prevalence of dropouts from a pulmonary rehabilitation program in patients with chronic obstructive pulmonary disease. Respir Med. 2022;193: 106742.

    Article  PubMed  Google Scholar 

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Acknowledgements

This work was partially supported by the use and resources of the Houston VA HSR&D Center for Innovations in Quality, Effectiveness and Safety (CIN13-413) and the South Central Mental Illness Research, Education and Clinical Center. The opinions expressed are those of the authors and not necessarily those of the Department of Veterans Affairs, the US Government, or Baylor College of Medicine.

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Authors and Affiliations

  1. Department of Physical Therapy, Azusa Pacific University, 701 East Foothill Boulevard, Azusa, CA, 91702, USA

    Abebaw Mengistu Yohannes

  2. McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA

    Jeff W. Jin

  3. HSR&D Center for Innovations in Quality, Effectiveness, and Safety, Michael E. DeBakey VA Medical Center, Houston, TX, USA

    Mark E. Kunik

  4. Baylor College of Medicine, Houston, TX, USA

    Mark E. Kunik

  5. South Central Mental Illness Research, Education, and Clinical Center, Michael E. DeBakey VA Medical Center, Houston, TX, USA

    Mark E. Kunik

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  1. Abebaw Mengistu Yohannes
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Correspondence to Abebaw Mengistu Yohannes.

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AMY contributed to the conceptualization of the review objectives and the development of an outline, completed the literature, and wrote the first draft. JWJ contributed to the conceptualization of the review objectives and the development of an outline, completed the literature, and wrote part of the first draft. MEK contributed to the conceptualization of the review objectives and the development of an outline and edited the first draft before submission. AMY, JWJ and MEK reviewed and edited the whole manuscript and approved the final submission.

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This work was also partially supported by the use and resources of the Houston VA HSR&D Center for Innovations in Quality, Effectiveness and Safety (CIN13-413) and the South Central Mental Illness Research, Education and Clinical Center.

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Abebaw Mengistu Yohannes, Jeff W. Jin, and Mark E. Kunik have no conflicts of interest to declare in relation to this manuscript.

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Yohannes, A.M., Jin, J.W. & Kunik, M.E. Benefit–Risk Assessment of Psychotropic Drugs in Older Patients with Chronic Obstructive Pulmonary Disease. Drugs Aging 39, 323–332 (2022). https://doi.org/10.1007/s40266-022-00935-0

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